Alzheimer's Disease (AD), the most common cause of dementia in the elderly, affects over 4 million Americans, a number projected to grow in coming decades; current overall costs for their care exceeds $100 billion per year. Current treatment options at best provide only temporary stabilization. Failures of clinical trials in AD have led to a focus on intervening earlier, when there is less structural damage to the brain. Characterizing and intervening in pre-dementia stages of AD is a research imperative. The UCSD Alzheimer's Disease Research Center (ADRC) has contributed greatly to research progress in the past 30 years. To continue to facilitate and conduct research into the causes, treatment and prevention of AD and related disorders, overall aims of this renewal application are: 1) To support research efforts by maintaining resources that include cohorts of subjects with normal cognition, Mild Cognitive Impairment (MCI), AD and other dementias (particularly Lewy Body Disease); neuropathology tissue from well-characterized subjects; biological samples (DNA, plasma and CSF); MRI and other brain images; and to maintain a comprehensive database. This will be carried out by six well- integrated Cores: Administrative, Clinical, Hispanic Satellite, Pathology, Outreach/Recruitment/Education (ORE) and Data Management/Biostatistics. 2) To support 3 research Projects: i) APP trafficking and endosomal sorting. ii) Probing SORL1 Risk Factors with Human Induced Pluripotent Stem Cell Technology; iii) Disease Mechanisms in Frontotemporal Dementia Linked to C9orf72 Expansion. Three Pilot Project awards related to Alzheimer's disease, aging or neurodegeneration will also be issued each year. 3) Interact widely with researchers at UCSD, the VA Medical Center, and nearby research institutions (Salk Institute, Scripps Research Institute, Sanford-Burnham Institute, and San Diego State University). 4) To collaborate with other AD Centers, NACC, and other national research efforts. The ADRC will follow about 500 subjects, using annual standardized evaluations that include the Uniform Data Set components. The ADRC will provide data to the National Alzheimer's Coordinating Center, and DNA to NCRAD. ADRC subjects will be offered participation in clinical trials organized by the Alzheimer's Disease Cooperative Study (ADCS) and by pharmaceutical companies, and participation in biomarker studies such as ADNI and PPMI. We will share subjects, data, brain images and biosamples with other researchers. 5) To continue to support innovative research, and to train new investigators 6) To foster professional education and training, and to improve public knowledge and awareness about aging and AD, as well as to provide innovative support efforts for patients and families affected by AD.